Table_2_Identification of potential Mitogen-Activated Protein Kinase-related key genes and regulation networks in molecular subtypes of major depressive disorder.XLS

BackgroundMajor depressive disorder (MDD) is a heterogeneous and prevalent mental disorder associated with increased morbidity, disability, and mortality. However, its underlying mechanisms remain unclear.
Materials and methodsAll analyses were conducted based on integrated samples from the GEO database. Differential expression analysis, unsupervised consensus clustering analysis, enrichment analysis, and regulation network analysis were performed.
ResultsMitogen-activated protein kinase (MAPK) signaling pathway was identified as an associated pathway in the development of MDD. From transcriptional signatures, we classified the MDD patients into two subgroups using unsupervised clustering and revealed 13 differential expression genes between subgroups, which indicates the probably relative complications. We further illustrated potential molecular mechanisms of MDD, including dysregulation in the neurotrophin signaling pathway, peptidyl-serine phosphorylation, and endocrine resistance. Moreover, we identified hub genes, including MAPK8, TP53, and HRAS in the maintenance of MDD. Furthermore, we demonstrated that the axis of miRNAs-TFs-HRAS/TP53/MAPK8 may play a critical role in MDD.
ConclusionTaken together, we demonstrated an overview of MAPK-related key genes in MDD, determined two molecular subtypes, and identified the key genes and core network that may contribute to the procession of MDD.

背景：重度抑郁症（Major Depressive Disorder, MDD）是一种异质性高、患病率广泛的精神障碍，与更高的发病率、致残率及死亡率密切相关，但其潜在发病机制仍未明确。
材料与方法：本研究所有分析均基于GEO数据库的整合样本开展，依次实施了差异表达分析、无监督共识聚类分析、富集分析及调控网络分析。
结果：丝裂原活化蛋白激酶（Mitogen-activated Protein Kinase, MAPK）信号通路被鉴定为与MDD发生发展相关的通路。基于转录组特征，我们通过无监督聚类将MDD患者划分为两个亚组，并鉴定出两亚组间存在13个差异表达基因，提示二者可能存在相关并发症差异。本研究进一步阐明了MDD的潜在分子机制，包括神经营养因子信号通路失调、肽丝氨酸磷酸化异常及内分泌抵抗。此外，我们还鉴定出维持MDD发病进程的核心基因，包括MAPK8、TP53及HRAS。进一步证实miRNAs-转录因子（Transcription Factors, TFs）-HRAS/TP53/MAPK8调控轴可能在MDD中发挥关键作用。
结论：综上，本研究系统梳理了MDD中与MAPK相关的关键基因概况，确定了两种分子亚型，并鉴定出可能参与MDD发病进展的关键基因及核心调控网络。